Melatonin is the main hormone involved in the neuroendocrine-immune axis. It also presents antitumour activity. To evaluate the role of melatonin on the progression of Walker-256 tumour in rats we determined the effect of the hormone on some biochemical and functional aspects of macrophage and lymphocytes from cachectic rats. An important finding observed in immune cells from tumour-bearing (TB) rats is the impairment on glutamine and glucose metabolism in such cells. These changes are very similar to those observed in pinealectomized rats (PNX). The increased production of lactate and the flux of glucose through the Krebs cycle and the reduction in glutamine consumption seems to be involved in the immunosuppression presented in the TB and PNX animals. Melatonin treatment restored the changes observed in the metabolism of glucose and glutamine and stimulated the proliferation of lymphocytes from tumour-bearing rats. The results indicate that the effect of melatonin upon tumour growth involves the stimulation of the immune system by the hormone.